Reversible changes in tumor growth and metastatic behavior induced by immune pressure.
Prolonged exposure to host immunity was studied for its effect on several characteristics of a cloned 3-methylcholanthrene-induced fibrosarcoma. One million cells of a clone 10-O were injected subcutaneously into normal C3H/HeJ mice (clone 10-N) or tumor-immune mice (clone 10-I). After 10 passages in immune mice, 1 X 10(6) cells from 10-I tumor were transferred back into normal mice (clone 10-R). After 5 to 10 additional in vivo passages, clone 10-O, 10-N, 10-I, and 10-R tumors were transplanted into normal mice and observed for tumor growth rate, tumorigenicity, antigen specificity, metastatic potential, and plating efficiency. Clone 10-I after 10 passages in immunized mice grew significantly more slowly than did 10-O or 10-N clones, required more tumor cells to cause 50% tumor incidence in normal mice (tumorigenicity), and completely lost its capacity to metastasize spontaneously or experimentally. The plating efficiency in vitro of 10-I was also less than that of 10-O or 10-N. All these changes reversed after 5 to 10 passages of 10-I clone back into normal mice (10-R). Although immune pressure induced qualitative antigenic changes, as demonstrated by a tumor-rejection assay, and resulted in no cross-reactivity with control tumor clones (antigen specificity), the degree of immune response to its autologous clone in immune mice (immunogenicity) remained constant. These results suggest that several unrelated characteristics of this clone 10 can be phenotypically changed during the same period by immune pressure.
Yu
S
S
Department of Surgery, Yale University, New Haven, Conn.
McKhann
C F
CF
Flye
M W
MW
D000671:Amputation, Surgical; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002999:Clone Cells; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis; D012513:Sarcoma, Experimental / Q000276:immunology / Q000473:pathology* / Q000601:surgery